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Alternative models for transgenerational epigenetic inheritance:Molecular psychiatry beyond mice and man

World Journal of Psychiatry 2021年第10期11卷 711-735页

作者： Gary R Hime sophie la stonehouse Terence Y Pang Department of Anatomy and Physiology The University of MelbourneParkville 3010VICAustralia Mental Health Theme The Florey Institute of Neuroscience and Mental HealthParkville 3052VICAustralia

Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent *** field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations,and that has to be supported by a continuous growth in *** majority of neuropsychiatric symptoms reflect complex geneenvironment interactions,with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of *** has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stressrelated behavioural phenotypes in both paternal and maternal lineages,providing further supporting evidence for heritability in ***,unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric *** rodents will remain the dominant model system for preclinical studies(especially for addressing complex behavioural phenotypes),there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate ***,we will discuss the utility and advantages of two alternative model organisms–Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.

关键词： Transgenerational inheritance Epigenetics Invertebrate models Caenorhabditis elegans Drosophila melanogaster Environmental stress

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New insights into the cell-and tissue-specificity of glucocorticoid actions

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Cellular & Molecular Immunology 2021年第2期18卷 269-278页

作者： Linda Quatrini sophie Ugolini Department of Immunology IRCCS Bambino GesùChildren’s HospitalRomeItaly Aix Marseille Univ CNRSINSERMCentre d’Immunologie de Marseille-LuminyMarseilleFrance

Glucocorticoids(GCs)are endogenous hormones that are crucial for the homeostasis of the organism and adaptation to the external *** of their anti-inflammatory effects,synthetic GCs are also extensively used in clinical ***,almost all cells in the body are sensitive to GC *** a result,these mediators have pleiotropic effects,which may be undesirable or detrimental to human ***,we summarize the recent findings that contribute to deciphering the molecular mechanisms downstream of glucocorticoid receptor *** also discuss the complex role of GCs in infectious diseases such as sepsis and COVID-19,in which the balance between pathogen elimination and protection against excessive inflammation and immunopathology needs to be tightly *** understanding of the cell type-and context-specific actions of GCs from the molecular to the organismal level would help to optimize their therapeutic use.

关键词： Glucocorticoids inflammation immune response

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Inflammation in Mental Disorders:Is the Microbiota the Missing Link?

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Neuroscience Bulletin 2020年第9期36卷 1071-1084页

作者： sophie Ouabbou Ying He Keith Butler Ming Tsuang Department of Psychiatry and National Clinical Research Center for Mental Disordersand Hunan Key Laboratory of Psychiatry and Mental HealthThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Human Microbiome Research Program Faculty of MedicineUniversity of Helsinki00290 HelsinkiFinland Cellular and Molecular Biology Research Centre University of Costa RicaSan Jose´11501Costa Rica Center for Behavioral Genomics Department of PsychiatryInstitute for Genomic MedicineUniversity of California San DiegoLa JollaCA 92093USA Harvard Institute of Psychiatric Epidemiology and Genetics Harvard School of Public HealthBostonMA 02115USA

Research suggests that inflammation is important in the pathophysiology of mental *** addition,a growing body of evidence has led to the concept of the microbiota-gut-brain *** understand the potential interactions,we begin by exploring the liaison between the immune system and mental disorders,then we describe the evidence that the microbiota impact the immune response in the developing ***,we review the literature that has documented microbiome alterations in major mental *** end with a summary of therapeutic applications,ranging from psycho-biotics to immunomodulatory drugs that could affect the microbiotagut-brain axis,and potential treatments to alleviate the adverse effects of antipsycho *** conclude that there is promising evidence to support the position that the microbiota plays an important role in the immunological pathophysiology of mental disorders with an emphasis on psychotic disorders and mood ***,more research is needed to elucidate the mechanisms.

关键词： Mental disorder Microbiota Immunology Neurodevelopment

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Egg CD9 protein tides correlated with sperm oscillations tune the gamete fusion ability in mammal

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Journal of Molecular Cell Biology 2018年第6期10卷 494-502页

作者： Benjamin Ravaux sophie Favier Eric Perez and Christine Gourier laboratoire de Physique Statistique Ecole Normale Superieure/PSL Research UniversityUPMC Univ Paris 06Universite Paris DiderotCNRS75005 ParisFrance

Mammalian fertilization involves membrane events-adhesion,fusion,sperm engulfment,membrane block to polyspermy-whose causes remain largely ***,specific oscillations of the sperm in contact with the egg were shown to be necessary for *** a microfluidic chip to impose the venue for the encounter of two gametes allowed real-time observation of the membrane remodelling occurring at the sperm/egg *** spatiotemporal mapping of egg CD9 revealed that this protein concentrates at the egg/sperm interface as a result of sperm oscillations,until a CDg-rich platform is nucleated on which fusion immediately takes *** 2-5 min after fusion,most of the CD9 leaves the egg for the external aqueous *** an egg membrane wave engulfs the sperm head in^25 *** results show that sperm oscillations initiate the CD9 recruitment that causes gamete fusion after which CD9 and associated proteins leave the membrane in a process likely to contribute to block *** highlight that the gamete fusion story in mammals is an unexpected interplay between mechanical constraints and proteins.

关键词： mammalian fertilization membrane dynamics real-time imaging CDg sperm oscillations gamete fusion

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Earwig mothers consume the feces of their juveniles during family life

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Insect Science 2022年第2期29卷 595-602页

作者： sophie Van Meyel Séverine Devers Joël Meunier Institut de Recherche sur la Biologie de l'Insecte UMR 7261CNRSUniversity of ToursToursFrance

Many animals consume the feces of their *** allo-coprophagy can have benefits,such as access to nutrients and symbionts,but also risks for consumers,mainly due to direct contact with pathogens that develop on *** the European earwig Forficula auricularia,mothers and juveniles live in nests lined with their *** surprising habit allows juveniles to consume the feces of their siblings during family life and provides them with nutritional benefits when mothers provide low ***,it was unclear whether earwig mothers also practice allo-coprophagy,and whether this behavior is motivated by their nutritional ***,we set up four types of experimental families in which we manipulated the nutritional needs of mothers and/or juveniles and measured the effects on the production of feces by the juveniles,and the consumption of these feces by the *** results first show that fed juveniles produced more feces pellet in presence of fed compared to food-deprived *** also found that,overall,about 50%of the mothers consumed juveniles *** consumption was both more likely and larger when the feces were produced by fed compared to food-deprived juveniles,while the proportion of feces pellets eaten was larger in food-deprived compared to fed ***,our results reveal that allo-coprophagy involves every family member and suggest that it can have both nutritional and non-nutritional benefits for earwig ***-coprophagy could thus favor the maintenance of mothers in the nest and,more generally,promote the early evolution of family life.

关键词： cooperation coprophagy dermaptera family life parental care

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Host cell protein quantification workflow using optimized standards combined with data-independent acquisition mass spectrometry

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Journal of Pharmaceutical Analysis 2023年第5期13卷 494-502页

作者： Steve Hessmann Cyrille Chery Anne-sophie Sikora Annick Gervais Christine Carapito BioOrganic Mass Spectrometry laboratory(LSMBO) IPHC UMR 7178University of StrasbourgCNRSProFI-FR2048Strasbourg67000France Department of Analytical Development Sciences for Biologicals UCB Pharma S.A.Braine l'Alleud1420Belgium

Monitoring of host cell proteins(HCPs)during the manufacturing of monoclonal antibodies(mAb)has become a critical requirement to provide effective and safe drug ***-linked immunosorbent assays are still the gold standard methods for the quantification of protein ***,this technique has several limitations and does,among others,not enable the precise identification of *** this context,mass spectrometry(MS)became an alternative and orthogonal method that delivers qualitative and quantitative information on all identified ***,in order to be routinely implemented in biopharmaceutical companies,liquid chromatography-MS based methods still need to be standardized to provide highest sensitivity and robust and accurate ***,we present a promising MS-based analytical workflow coupling the use of an innovative quantification standard,the HCP Profiler solution,with a spectral library-based data-independent acquisition(DIA)method and strict data validation *** performances of the HCP Profiler solution were compared to more conventional standard protein spikes and the DIA approach was benchmarked against a classical datadependent acquisition on a series of samples produced at various stages of the manufacturing *** we also explored spectral library-free DIA interpretation,the spectral library-based approach still showed highest accuracy and reproducibility(coefficients of variation<10%)with a sensitivity down to the sub-ng/mg mAb ***,this workflow is today mature to be used as a robust and straightforward method to support mAb manufacturing process developments and drug products quality control.

关键词： Host cell proteins Absolute quantification standards Data-independent acquisition

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Reconfigurable single-shot incoherent optical signal processing system for chirped microwave signal compression

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Science Bulletin 2017年第4期62卷 242-248页

作者： Ming Li Shuqian Sun Antonio Malacarne sophie laRochelle Jianping Yao Ninghua Zhu Jose Azana Institut National de la Recherche Scientifique-Energie Materiaux et Telecommunications(INRS-EMT)VarennesQuebec J3X 1S2Canada State Key laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China University of Chinese Academy of Sciences Beijing 100049China TeCIP Institute Scuolo Superiore Sant'AnnaPisa 56124Italy Center for Optics Photonics and Laser(COPL)Universite LavalQuebec G1V OA6Canada Microwave Photonics Research laboratory University of OttawaOntario K1N 6N5Canada

We propose and demonstrate a reconfigurable and single-shot incoherent optical signal processing system for chirped microwave signal compression, using a programmable optical filter and a multiwavelength laser(MWL). The system is implemented by temporally modulating a specially shaped MWL followed by a suitable linear dispersive medium. A microwave dispersion value up to 1.33 ns/GHz over several GHz bandwidth is achieved based on this approach. Here we demonstrate a singleshot compression for different linearly chirped microwave signals over several GHz bandwidth. In addition, the robustness of the proposed system when input RF signals are largely distorted is also discussed.

关键词： Fourier optics and signal processingAnalog optical signal processing Radio frequency photonics Pulse compression

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Very high conservation between Cyp6a2 from Drosophila melanogaster and its ortholog Cyp6a26 from D. simulans

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Insect Science 2007年第1期14卷 15-27页

作者： sophie TARES laURY ARTHAUD ALEXANDRA BRUN-BARALE DIDIER CROCHARD JEAN-MARC BRIDE MARCEL AMICHOT Institut National de la Recherche Agronomique UMR ROSE 1112 Sophia-Antipolis France

Although Drosophila simulans is closely related to D. melanogaster, very few cytochrome P450 genes have been studied in this species until now. As Cyp6a2 from D. melanogaster is a major gene implicated in the detoxification of xenobiotic molecules, we decided to look for its ortholog in D. simulans. The isolated gene, Cyp6a26, presents structural characteristics very similar to those of Cyp6a2： an identical size of 1590-bp comprising two exons separated by a 69-bp intron and a nucleotide sequence homology of 95%. Many putative transcriptionally important motifs were identified in the upstream DNAs of the two genes but only 16 elements are in common positions. Treatment of flies with phenobarbital leads to an increased production of Cyp6a26 mRNAs. The expression of Cyp6a26 mRNAs varies following developmental stages in the same manner as Cyp6a2. Immunohistochemistry experiments of phenobarbital-treated adult drosophila show that the spatial expression pattern of the two proteins is also conserved between the two species. All these data argue in favor of the conservation of the function of these homologous genes between the two Drosophila species.

关键词： cytochrome P450 Drosophila ortholog mRNA expression promotor

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Immature and mature antibodies as defenders against cancer

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Cellular & Molecular Immunology 2023年第1期20卷 3-5页

作者： Robin V.lacombe sophie Sibéril Jordan D.Dimitrov Centre de Recherche des Cordeliers INSERMCNRSSorbonne UniversitéUniversitéParis CitéParisFrance

Antibodies(Abs)are glycoprotein molecules that represent an essential component of the adaptative immune *** are secreted in body fluids and act as a critical part of immune *** recognition of self-antigens by Abs is normally selected against during B-cell development,autoreactive Abs can be generated as a result of pathological immune responses,as observed in autoimmune *** can also be produced in cancer patients,where they may have beneficial roles[1].Indeed,the presence of intratumoral antibody-secreting cells(ASCs)and B-cell-rich tertiary lymphoid structures(TLSs)has been observed in many cancer types and generally correlates with a favorable clinical prognosis[2,3,4,5,6].The existence of specific antitumor antibody responses suggests that tumor cells express molecules that are recognized as nonself antigens by the immune system or that tolerance of self-antigens expressed on cancer cells is lost[1,4].The study of the origin of tumor-reactive Abs and their specificity and functions is of paramount importance for understanding the development of adaptive antitumor immune responses and for revealing novel therapeutic avenues.A recent publication in Cell by Mazor et al.[7]has provided an important advance in our understanding of antibody responses in *** particular,this work paves the way for the distinction between antibody-reactive tumors and antibody-nonreactive tumors,which is reminiscent of the dichotomy of the noninfiltrated“cold”tumor microenvironment(TME)in contrast with the highly infiltrated with immune cells“hot”TME[8].Moreover,an important finding of the study was the demonstration that tumor-directed autoreactivity may be either preexisting or induced by somatic hypermutations,a mechanism related to the chronicity of cancer.

关键词： cancer antibodies specificity

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IgH locus suicide recombination does not depend on NHEJ in contrast to CSR in B cells

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Cellular & Molecular Immunology 2019年第2期16卷 201-202页

作者： Hend Boutouil François Boyer Jeanne Cook-Moreau Michel Cogné sophie Péron CRIBL UMR CNRS 7276 INSERM U126287000 LimogesFrance Institut Universitaire de France 75000 ParisFrance

IgH locus suicide recombination(LSR)occurs in activated Blymphocytes and may result in the death of the concerned B cell,justifying the name“locus suicide recombination”.1 LSR,as for immunoglobulin(Ig)class switch recombination(CSR),is an intrachromosomal recombination in the Ig heavy chain(IgH)***,LSR somehow appears to be the detrimental counterpart of CSR in activated B cells,since CSR intends for cells to actively participate in immune responses while LSR eliminates B ***,an important question to address is the regulation and the exact molecular mechanism of LSR.

关键词： CSR eliminate concerned

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